Modulation of the long terminal repeat promoter activity of small ruminant lentiviruses by steroids

• Hormones may be involved in the intermittent shedding of small ruminant lentiviruses (SRLVs).
• The U3-cap region of the retroviral long terminal repeat (LTR) contains hormone responsive elements.
• The effects of progesterone, cortisol and dehydroepiandrosterone (DHEA) on viral expression were analysed.
• Generally, high concentrations of steroids inhibited expression of SRLVs.
• However, physiological concentrations of cortisol or DHEA increased expression of SRLVs.

Production and excretion of small ruminant lentiviruses (SRLVs) varies with the stage of the host reproductive cycle, suggesting hormonal involvement in this variation. Stress may also affect viral expression. To determine if hormones affect SRLV transcriptional activity, the expression of green fluorescent protein (GFP) driven by the promoters in the U3-cap region of the long terminal repeats (LTRs) of different strains of SRLV was assessed in cell culture. High concentrations of steroids (progesterone, cortisol and dehydroepiandrosterone) inhibited expression of GFP driven by SRLV promoters. This effect decreased in a dose-dependent manner with decreasing concentrations of steroids. In some strains, physiological concentrations of cortisol or dehydroepiandrosterone (DHEA) induced the expression of GFP above the baseline. There was strain variation in sensitivity to hormones, but this differed for different hormones. The presence of deletions and a 43 base repeat in the U3 region upstream of the TATA box of the LTR made strain EV1 less sensitive to DHEA. However, no clear tendencies or patterns were observed when comparing strains of different genotypes and/or subtypes, or those triggering different forms of disease.